By using a combined experimental and theoretical approach, we have gained new insights into multivalent binding. We have elucidated a novel 'sacrifice and screening’ effect in which flexible multivalent arrays optimise their interactions with DNA, and dissected the thermodynamic parameters leading us to conclude that multivalent charge‐display is crucial. By modifying the dendron focal point we achieved the self‐assembly of supramolecular dendrimers with multivalent ligand arrays which were demonstrated to bind DNA much more effectively than non‐assembling analogues. The self‐organising hydrophobic units tune the overall surface charge of the self‐assembled nanostructures and hence control the multivalent interactions with the binding partner. We have also shown how degradability can be built into these systems – important for biological applications. Finally, we have studied different biological targets. This has allowed us to generate self‐assembling multivalent systems with high affinity for heparin, and our work with RGD peptides has demonstrated that the self‐assembly approach to multivalency is competitive in terms of binding affinity with a full dendritic approach. This chapter demonstrates that the combination of experiment and theory is powerful for providing fundamental insight into nanoscale recognition and will underpin potential future applications in nanomedicine.

From Multivalent Dendrons to Self‐asssembled Multivalent Dendrimers: a Combined Experimental and Theoretical ApproachDendrimers in Biomedical Applications

PRICL, SABRINA
2013

Abstract

By using a combined experimental and theoretical approach, we have gained new insights into multivalent binding. We have elucidated a novel 'sacrifice and screening’ effect in which flexible multivalent arrays optimise their interactions with DNA, and dissected the thermodynamic parameters leading us to conclude that multivalent charge‐display is crucial. By modifying the dendron focal point we achieved the self‐assembly of supramolecular dendrimers with multivalent ligand arrays which were demonstrated to bind DNA much more effectively than non‐assembling analogues. The self‐organising hydrophobic units tune the overall surface charge of the self‐assembled nanostructures and hence control the multivalent interactions with the binding partner. We have also shown how degradability can be built into these systems – important for biological applications. Finally, we have studied different biological targets. This has allowed us to generate self‐assembling multivalent systems with high affinity for heparin, and our work with RGD peptides has demonstrated that the self‐assembly approach to multivalency is competitive in terms of binding affinity with a full dendritic approach. This chapter demonstrates that the combination of experiment and theory is powerful for providing fundamental insight into nanoscale recognition and will underpin potential future applications in nanomedicine.
9781849736114
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2760966
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